title: Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial.
abstract: BACKGROUND
  Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.
  
  
  METHODS
  This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.
  
  
  CONCLUSIONS
  The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.
  
  
  BACKGROUND
  Clinical Trials NCT00970931.
authors.affiliation: Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. ffuchs@hcpa.ufrgs.br
authors.forename: Flávio D
authors.initials: FD
authors.lastname: Fuchs
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Fuchs
authors.forename: Leila B
authors.initials: LB
authors.lastname: Moreira
authors.forename: Miguel
authors.initials: M
authors.lastname: Gus
authors.forename: Antônio C
authors.initials: AC
authors.lastname: Nóbrega
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Poli-de-Figueiredo
authors.forename: Décio
authors.initials: D
authors.lastname: Mion
authors.forename: Luiz
authors.initials: L
authors.lastname: Bortoloto
authors.forename: Fernanda
authors.initials: F
authors.lastname: Consolim-Colombo
authors.forename: Fernando
authors.initials: F
authors.lastname: Nobre
authors.forename: Eduardo Barbosa
authors.initials: EB
authors.lastname: Coelho
authors.forename: José F
authors.initials: JF
authors.lastname: Vilela-Martin
authors.forename: Heitor
authors.initials: H
authors.lastname: Moreno
authors.forename: Evandro José
authors.initials: EJ
authors.lastname: Cesarino
authors.forename: Roberto
authors.initials: R
authors.lastname: Franco
authors.forename: Andréa Araujo
authors.initials: AA
authors.lastname: Brandão
authors.forename: Marcos R
authors.initials: MR
authors.lastname: de Sousa
authors.forename: Antônio Luiz Pinho
authors.initials: AL
authors.lastname: Ribeiro
authors.forename: Paulo Cesar
authors.initials: PC
authors.lastname: Jardim
authors.forename: Abrahão Afiune
authors.initials: AA
authors.lastname: Neto
authors.forename: Luiz César N
authors.initials: LC
authors.lastname: Scala
authors.forename: Marco
authors.initials: M
authors.lastname: Mota
authors.forename: Hilton
authors.initials: H
authors.lastname: Chaves
authors.forename: João Guilherme
authors.initials: JG
authors.lastname: Alves
authors.forename: Dario C Sobral
authors.initials: DC
authors.lastname: Filho
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pereira e Silva
authors.forename: José A Figueiredo
authors.initials: JA
authors.lastname: Neto
authors.forename: Maria Cláudia
authors.initials: MC
authors.lastname: Irigoyen
authors.forename: Iran
authors.initials: I
authors.lastname: Castro
authors.forename: André Avelino
authors.initials: AA
authors.lastname: Steffens
authors.forename: Rosane
authors.initials: R
authors.lastname: Schlatter
authors.forename: Renato Bandeira
authors.initials: RB
authors.lastname: de Mello
authors.forename: Francisca
authors.initials: F
authors.lastname: Mosele
authors.forename: Flávia
authors.initials: F
authors.lastname: Ghizzoni
authors.forename: Otávio
authors.initials: O
authors.lastname: Berwanger
mesh_terms: D000328:Adult; D000368:Aged; D000584:Amiloride / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001938:Brazil; D002752:Chlorthalidone / Q000627:therapeutic use*; D004232:Diuretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D058246:Prehypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D004338:Drug Combinations; D000584:Amiloride; D002752:Chlorthalidone